Incidence and management of secondary deformities after megaendoprosthetic proximal femur replacement in skeletally immature bone sarcoma patients.

INTRODUCTION: Megaendoprosthetic reconstruction of bone defects in skeletally immature patients has led to the development of unique complications and secondary deformities not observed in adult patient cohorts. With an increasing number of megaendoprosthetic replacements performed, orthopedic oncologists still gain experience in the incidence and type of secondary deformities caused. In this study, we report the incidence, probable cause and management outcome of two secondary deformities after megaendoprosthetic reconstruction of the proximal femur: hip dysplasia and genu valgum. MATERIALS AND METHODS: Retrospective analysis of 14 patients who underwent primary and/or repeat reconstruction/surgery with a megaendoprosthetic proximal femur replacement between 2018 and 2022. RESULTS: Mean patient age was 9.1 years (range 4-17 years). Stress shielding was observed in 71.4%. Hip dislocation was the most frequent complication (50%). While four dislocations occurred without an underlying deformity, secondary hip dysplasia was identified in 58.3% (n = 7/12) of intraarticular resections and reconstructions, leading to dislocation in 71.4% (n = 5/7). A genu valgum deformity was observed in 41.6% (n = 5/12). The incidence of secondary hip dysplasia and concomitant genu valgum was 42.9% (n = 3/7). Triple pelvic osteotomy led to rebound hip dysplasia in two cases (patients aged < 10 years), whereas acetabular socket replacement led to stable hip joints over the course of follow-up. Temporary hemiepiphyseodesis was applied to address secondary genu valgum. CONCLUSIONS: Patients aged < 10 years were prone to develop secondary hip dysplasia and genu valgum following proximal femur replacement in this study. Management of secondary deformities should depend on remaining skeletal growth. Stress shielding was observed in almost all skeletally immature patients.

Prognostic Factors for Leiomyosarcoma with Isolated Metastases to the Lungs: Impact of Metastasectomy.

BACKGROUND: Leiomyosarcoma (LMS) most frequently metastasizes to the lung. Metastatic LMS is considered incurable. Selected patients may benefit from pulmonary metastasectomy (PM) within multimodal therapy. This study analyzed the prognostic relevance of clinicopathologic factors in these patients. METHODS: Patients with metastatic LMS to the lung treated in our center from 2004 to 2020 were included in this single-center retrospective study. Overall survival (OS), progression-free survival (PFS), and prognostic factors were analyzed. RESULTS: The study had 64 patients (33 males, 52%) with metastatic LMS to the lung. The 5-year OS was 55% after the diagnosis of pulmonary metastases. Age older than 60 years at the primary tumor diagnosis, primary tumor larger than 70 mm, and five or more lung metastases were associated with poorer OS. Of the 64 patients, 44 underwent PM. The postoperative mortality rate was 0%. The patients selected for PM were younger and had smaller primary tumors, fewer metastases, and metastases that more often were metachronous. Metastasis grade (G1 vs. G2/3) and size (20-mm cutoff) were significant prognostic factors for OS (p = 0.05) and PFS (p = 0.028) after PM, respectively. The 44 patients who underwent PM had a survival benefit compared with the patients who were selected but did not undergo PM (n = 6) and the patients who were not selected for PM (n = 14). Three patients (7%) were alive and free of disease at the last follow-up visit respectively 5.5, 9, and 12 years after PM. CONCLUSIONS: For patients with leiomyosarcoma, PM is safe. Despite aggressive multimodal treatment, most patients will experience recurrence and eventually die of their disease. However, a small subgroup of patients could potentially be cured after PM.

Reconstruction survival of segmental megaendoprostheses: a retrospective analysis of 28 patients treated for intercalary bone defects after musculoskeletal tumor resections.

INTRODUCTION: Intercalary endoprosthetic reconstructions have been reserved for patients with a limited life expectancy due to reports of high rates of early mechanical and reconstruction failure. MATERIALS AND METHODS: In this study, we retrospectively analyzed 28 patients who underwent intercalary endoprosthetic reconstruction of the femur (n = 17) or tibia (n = 11) regarding reconstruction survival and causes of complications and reconstruction failure. RESULTS: A total of 56 stems were implanted in this collective, 67.9% of which were implanted using cementation. Eight different stem designs were implanted. The mean patient age at the time of operation was 42.3 years. The mean bone defect needing reconstruction measured 18.5 cm. Resection margins were clear in 96.4% of patients. Of twenty-six complications, five were not implant-associated. We observed infection in 10.7% (n = 3) and traumatic periprosthetic fracture in 3.6% (n = 1) of cases. The most frequent complication was aseptic stem loosening (ASL) (53.8%; n = 14) occurring in eight patients (28.6%). The metaphyseal and meta-diaphyseal regions of femur and tibia were most susceptible to ASL with a rate of 39.1% and 31.3% respectively. No ASLs occurred in epiphyseal or diaphyseal location. Overall reconstruction survival was 43.9% and 64.3% including patients who died of disease with their implant intact. Overall limb survival was 72.7%. CONCLUSIONS: Proper planning of segmental reconstructions including stem design with regard to unique anatomical and biomechanical properties is mandatory to address the high rates of ASL in metaphyseal and metadiaphyseal stem sites. With continued efforts of improving stem design in these implantation sites and decreasing rates of mechanical failure, indications for segmental megaendoprostheses may also extend to younger patients with the localized disease for their advantages of early weight bearing and a lack of donor-site morbidity.

Pain in survivors of Ewing sarcoma: Prevalence, associated factors and prediction of recurrence.

BACKGROUND: While the prognosis of patients with Ewing sarcoma (EwS) is improving, little is known about the frequency of pain and its risk factors in survivors of EwS. This study aims to analyse the prevalence and risk factors of pain and its predictive value for recurrence. PATIENTS AND METHODS: In patients with remission after treatment of EwS, frequency and characteristics of pain within the first 5 years of follow up were assessed retrospectively. RESULTS: Of 80 patients, 37 (46%) presented with at least one episode of pain. Chronic pain (>3 months) was observed in 10 patients (13%). Experience of at least one episode of pain was associated with prior combined local treatment (surgery and radiation compared to surgery alone; odds ratio [OR] 5.83, 95% confidence interval [CI] 1.43-34.9, P = .007). A total of 59 episodes of pain were observed, including 47 acute and 12 chronic episodes. Lower limb pain accounted for 46% (27/59) of all episodes of pain, and was associated with primary tumour of the pelvis or lower extremity (OR 4.29, 95% CI 1.18-18.21, P = .025), which represented 64% (51/80) of all EwS. The positive predictive value of pain for recurrence was only 12%. CONCLUSION: Pain is a common problem in survivors of EwS, which mostly affects the lower extremity, and should be regularly assessed. Interventions to reduce pain may be particularly important in patients with combined local treatment with surgery and radiation, who seem to be at considerably increased risk for pain. Patients presenting with pain should be examined for recurrence.

[Strategic approach to pathological fractures]. / Strategisches Vorgehen bei pathologischen Frakturen.

Pathological tumor-associated fractures are overall rare. They can occur in every age group and every bone. Although tumor-related fractures only form a small proportion of bone fractures, the early recognition of the cause of the fracture and treatment according to oncological guidelines are of enormous importance for affected patients. False treatment is frequently associated with far-reaching negative consequences with respect to the course of the disease. The great challenge is not the expeditious surgical treatment but much more the adequate diagnostics and the incorporation of local fracture treatment into an interdisciplinary overall oncological concept.

Silver-coated megaprostheses in the proximal femur in patients with sarcoma.

BACKGROUND: Proximal femur replacements in patients with sarcoma are associated with high rates of infection. This study is the largest one comparing infection rates with titanium versus silver-coated megaprostheses in sarcoma patients. METHODS: Infection rates were assessed in 99 patients with proximal femur sarcoma who underwent placement of a titanium (n = 35) or silver-coated (n = 64) megaprosthesis. Treatments administered for infection were also analyzed. RESULTS: Infections occurred in 14.3% of patients in the titanium group, in comparison with 9.4% of those in the silver group, when the development of infection was the primary end point. The 5- and 10-year event-free survival rates for the prosthesis relative to the parameter of infection were 90% in the silver group and 83% in the titanium group. The overall infection rates were 10.9% in the silver group and 20% in the titanium group. Two patients each in the silver and titanium groups ultimately had to undergo amputation. The need for two-stage prosthesis exchanges (57.1% in the titanium group) declined to 14.3% in the silver group. CONCLUSION: Using a silver-coated proximal femoral replacement nearly halved the overall infection rate. When infections occurred, it was usually possible to avoid two-stage prosthesis exchanges in the silver group.

Tumour endoprosthesis replacement in the proximal tibia after intra-articular knee resection in patients with sarcoma and recurrent giant cell tumour.

PURPOSE: Proximal tibia replacements are commonly associated with post-operative complications and poor functional results due to an insufficiency of the extensor mechanism. METHODS: This study evaluated the clinical results with a special emphasis of the extensor mechanism reconstruction with a reattachment tube and complications after intra-articular resection of the proximal tibia and reconstruction with a tumour endoprosthesis (MUTARS®) in 98 patients (median age 18 years) with malignant bone tumours or giant cell tumours. RESULTS: Kaplan-Meier analysis showed that the limb survival rates were 94.9, 90.5 and 74.5% at one, two and ten years, respectively. Periprosthetic infection was the most common reason for secondary amputation (eight patients). The cumulative incidence rates of prosthetic failure (Henderson II-IV) were 18% at two years and 29% at five years post-operatively. An active extension deficit of more than 10° was noted in six patients only. CONCLUSIONS: These results suggest that limb salvage with tumour prostheses after intra-articular resection can achieve good functional results with an active extension of the knee in the majority of patients. While mechanical complications can be treated successfully with revision surgery, periprosthetic infection continues to be the main reason for secondary amputation.

Silver-Coated Megaprosthesis of the Proximal Tibia in Patients With Sarcoma.

BACKGROUND: Proximal tibia arthroplasty is associated with high rates of infection. This study is the largest one that has compared the infection rates with titanium vs silver-coated megaprostheses in patients treated for sarcomas. METHODS: The infection rate in 98 patients with sarcoma or giant-cell tumor in the proximal tibia who underwent placement of a titanium (n = 42) or silver-coated (n = 56) megaprosthesis (MUTARS) was assessed, along with the treatments administered for any infection. RESULTS: As the primary end point of the study, the rates of infection were 16.7% in the titanium group and 8.9% in the silver group, resulting in 5-year prosthesis survival rates of 90% in the silver and 84% in the titanium group. Whereas in the titanium group 37.5% of patients ultimately had to undergo amputation in the present study, these mutilating surgical procedures were only necessary in the silver group in one patient (14.3%). CONCLUSION: The use of silver-coated prosthesis reduced the infection rate in a relatively large and homogeneous group of patients. In addition, less-aggressive treatment of infection was possible in the group with silver-coated prosthesis.

Silver-coated megaprostheses: review of the literature.

Periprosthetic infection remains one of the most serious complications following megaendoprostheses. Despite a large number of preventive measures that have been introduced in recent years, it has not been possible to further reduce the rate of periprosthetic infection. With regard to metallic modification of implants, silver in particular has been regarded as highly promising, since silver particles combine a high degree of antimicrobial activity with a low level of human toxicity. This review provides an overview of the history of the use of silver as an antimicrobial agent, its mechanism of action, and its clinical application in the field of megaendoprosthetics. The benefits of silver-coated prostheses could not be confirmed until now. However, a large number of retrospective studies suggest that the rate of periprosthetic infections could be reduced by using silver-coated megaprostheses.

Analysis of surgical and oncological outcome in internal and external hemipelvectomy in 34 patients above the age of 65 years at a mean follow-up of 56 months.

BACKGROUND: With an increasing life expectancy and improved treatment regimens for primary or secondary malignant diseases of soft tissue or bone, hemipelvectomy will have to be considered more often in elderly patients in the future. Scientific reviews concerned with the surgical and oncological outcome of elderly patients undergoing hemipelvectomy are scarce. Therefore, it is the purpose of this study to review the outcome of patients treated with that procedure at our hospital and investigate the feasibility of such extensive procedures at an increased age. METHODS: A retrospective analysis of thirty-four patients who underwent hemipelvectomy at an age of 65 years or older was performed to determine their surgical and oncological outcome. The Kaplan-Meier method was used to calculate the cumulative probability of survival using the day of tumor resection as a starting point. Univariate analysis was carried out to investigate the influence of a particular single parameter. RESULTS: The mean age at operation was 70.2 years. Thirty patients were treated for intermediate- to high-grade sarcoma and 81.8% of tumors were larger than or equal to 10 cm in the longest diameter. Thirteen patients underwent internal hemipelvectomy and nine patients external hemipelvectomy as a primary procedure. Twelve patients were treated with external hemipelvectomy after failed local tumor control at primary operation. Wound infection occurred in 61.7% of cases. Three patients underwent amputation for non-manageable infection after internal hemipelvectomy. Hospital mortality was 8.8%. Clear resection margins were obtained in 88% of patients; in another 6% of patients planned intralesional resections were performed. Local recurrence occurred in 8.8% of patients at a mean time of 26 months after operation. Eleven patients are alive with no evidence of disease and 23 patients died of disease or other causes. Patients with pulmonary metastases had a mean survival period after operation to DOD of 22 months compared to 37 months in the curative group. CONCLUSION: Despite an elevated rate in hospital mortality and wound infection, this study suggests that hemipelvectomy is feasible in elderly patients, although requiring long hospitalization periods and causing a limited functional outcome.

Improvement of the shoulder function after large segment resection of the proximal humerus with the use of an inverse tumour prosthesis.

PURPOSE: Active shoulder function after segmental tumour resection of the proximal humerus and endoprosthetic reconstruction is regularly compromised, while the overall arm function allows a satisfying use in daily activities. The main functional problem remains the loss of huge parts of the shoulder girdle musculature and its bony attachment. In revision arthroplasty inverse shoulder implants can improve the active range of motion significantly in comparison to anatomical shaped prostheses. The aim of this study was to investigate if these promising experiences are transferable to reconstructions after tumour resection of the proximal humerus by using a modular inverse tumour prosthesis. METHODS: In this study we observed the functional and oncological results of 18 inverse proximal humerus endoprosthetic replacements (IPHP) with the MUTARS system (Implantcast®) after resection of benign (1x giant cell) and malignant (11x primary bone sarcoma, 5x bone metastasis of carcinoma) bone tumours. Mean age at operation was 42 years. The mean postoperative follow-up was 33 months (range ten to 120). RESULTS: Resection margins were wide in 13 and marginal in five patients. Mean reconstruction length was 15.1 cm (range 6-25 cm). Mean operation time was 191 minutes. The axillary nerve was mostly preserved in 78 % (n = 14). At latest follow-up the patients presented a medium MSTS-score of 24.6/30. The mean active arm abduction in the shoulder joint was 78° and 88° active arm elevation for patients with intact axillary nerve function, but significantly reduced for the four patients with compromised deltoid function. One patient needed a surgical revision due to a deep implant infection. CONCLUSIONS: The IPHP offers a significant improvement of active shoulder function in patients in whom the axillary nerve can be preserved in comparison to anatomically-shaped implants. However, for patients without any deltoid function there is no benefit regarding an improved active range of motion using an IPHP.

Uncemented Customized Hollow Stems in Tumor Endoprosthetic Replacement-A Good Opportunity to Protect the Adjacent Joint in Children?

This study aimed to retrospectively analyze the follow-up results of cases in which the adjacent joint was preserved using a custom-made uncemented short-stem design (hollow stem) with optional external flanches in tumor endoprosthetic replacement due to bone sarcomas in 13 patients (with an average age of 9.6 years) between 2017 and 2023. Reconstructions were proximal femur (n = 6), intercalary femur (n = 4), intercalary tibia (n = 2), and proximal humerus (n = 1) tumor prostheses. The hollow body was used distally in 10 of the megaprotheses, proximally in 1, and both proximally and distally in 2 of them. The average distance from the joints was 6 cm in stems with flanches and 11.8 cm in stems without flanches. No aseptic loosening or deep infection was observed during an average follow-up of 34 months. Except for one case with a tibial intercalary prosthesis that needed a revision, all cases were well osteointegrated and all lower extremity cases could bear full weight without pain. In cases where the remaining bone stock after bone resection is insufficient for a standard stem implantation, reconstruction with a patient-specific short hollow-stem design appears to be a good alternative to protect healthy joints with high prosthesis survival and low revision rates in the short-term follow-up.

Slipped capital femoral epiphysis after tumor prosthesis implantation in a patient receiving chemotherapy.

While the usual etiology of slipped capital femoral epiphysis (SCFE) is idiopathic, there are many other factors that increase the predisposition to slippage. Chemotherapy can be one of them. In this article, we report a rare case of acute SCFE after tumor prosthesis implantation in a patient who received chemotherapy. A 10-year-old girl with osteosarcoma of the right distal femur underwent (neo-) adjuvant chemotherapy, wide tumor resection, and reconstruction using a growing tumor prosthesis and a short non-cemented femoral stem. Half a year after implantation, she developed aseptic loosening. Revision surgery was performed using a hydroxyapatite (HA)-coated cementless femoral stem. Postoperative plain radiographs revealed SCFE that was treated by closed reduction and screw fixation. The patient recovered without complications, and unaffected hip showed no radiographic signs of slippage on follow-up. The forces of implanting a tumor prosthesis, particularly with a non-cemented stem, can increase the risk of an acute SCFE. The controversy over prophylactic pinning of the uninvolved hip in chemotherapy-associated SCFE is unresolved. Pinning can be considered only in the presence of abnormal prodromal radiological findings.

Return to Sports and Activity in Tumor Orthopaedics. / Wiederkehr zu körperlicher Aktivität und Sport in der Tumororthopädie.

As survival rates associated with the multimodal treatment of malignant bone cancer (osteosarcoma and Ewing's sarcoma) are satisfactory, health-related quality of life and the return to activity and sports by the affected patients have attracted increasing attention in recent years. Nowadays, limbs can be salvaged for most patients using modular endoprostheses. Such patients are typically adolescents and young adults who have high activity levels and thereby high demands for multimodal cancer treatment. This study aimed to evaluate the activity levels and sporting proficiencies that can be attained after modular endoprosthetic treatment of bone sarcomas as well as the extent to which physiotherapeutic and sports interventions influence functional outcome and activity levels.This non-systematic review of the literature focused on the return to activity and sports after modular endoprosthetic treatment of lower extremities bone sarcomas in adolescents and young adults. The electronic database PubMed was screened for relevant publications on this issue. A treatment algorithm for return to activity and sports in tumor orthopaedics is proposed.The objective activity level (gait cycles per day and gait intensities) in patients treated for bone sarcomas is reduced in short- and long-term follow-ups compared with healthy controls and patients with other cancers (leukaemia). Although a negative impact is observed in terms of motor performance, it shows improvement over time. Functional assessment at 12 postoperative months is sensible as neoadjuvant chemotherapy is completed by then. In long-term follow-up, patients with bone sarcomas can achieve high sports activity levels, i.e., type of sport, frequency/week and UCLA score, after modular endoprosthetic reconstruction. The maximum level is attained at 5 years postoperatively. Nevertheless, there is a shift from high- and intermediate- to low-impact sports. Only 20% of the patients participate in school sports regularly without limitations. The localisation of bone sarcoma, but not the rate of postoperative complications, influences the postoperative activity level. Individualised sports-related interventions during and after multimodal treatment can improve the short-term activity levels; moreover, "serious games" can improve motor performance and postural control. There is no evidence that intense activity levels leads to early loosening of the endoprosthesis. There is insufficient valid data on activity and sports after modular endoprosthetic treatment of bone sarcomas of the upper extremities.High preoperative activity levels of young patients with bone sarcomas must be considered in tumour orthopaedics. Limitations on sports activities have a significant negative impact on the quality of life and mental health of such patients. Therefore, tumour orthopaedic treatment has to focus on preserving an improvement in these factors. The overall existing evidence concerning this issue is weak. Additional studies to evaluate the ability to return to specific sports activities are desirable, as well as prospective interventional studies.

Cortical Desmoid of the Distal Femur-Incidentaloma or Insertional Tendinopathy?

BACKGROUND: The cortical desmoid (DFCI) of the posteromedial femoral condyle is considered an asymptomatic incidental finding in adolescents without clinical relevance. The aim of this study was to evaluate the clinical relevance of DFCI from both a tumor orthopedic and sports medicine point of view. METHODS: n = 23 patients (13.74 ± 2.74 years; nineteen female, four male) with DFCI of the posteromedial femoral condyle were included. A localized posteromedial knee pain on exertion was differentiated from non-specific knee pain. Symptom duration, additional pathologies, number of MRIs, sports activity and training intensity, downtime, therapeutic modalities, and relief/remission of symptoms were documented. The Tegner activity scale (TAS) and Lysholm score (LS) were collected. The influence of specific posteromedial pain, MRI presence of paratendinous cysts, sports level as well as physiotherapy on downtime and LS/TAS was statistically analyzed. RESULTS: 100% reported knee symptoms at initial presentation. A localized posteromedial pain was documented in 52%. In 16/23 (70%) additional functional pathologies were diagnosed. Patients were physically highly active with high training intensities (6.52 ± 5.87 h/week) and performance level (65% competitive vs. 35% recreational). Patients underwent 1.91 ± 0.97 MRIs (max four). Symptom duration was 10.48 ± 11.02 weeks. A follow-up examination was performed after 12.62 ± 10.41 months (n = two lost to follow-up). 17/21 had physiotherapy, on average 17.06 ± 13.33 units. Overall downtime was 13.39 ± 12.50 weeks, the return-to-sports (RTS) rate 81%. 100%/38% reported a relief/remission of complaints. LS was 93.29 ± 7.95, median TAS before onset of knee complaints/at follow-up 7 (6-7)/7 (5-7). Specific posteromedial pain, presence of paratendinous cysts, sports level and physiotherapy had no significant influence on downtime and outcome parameters (n.s.). CONCLUSIONS: DFCI as a pathognomonic finding is recurrently encountered in the MRIs of children and adolescents. This knowledge is essential to spare patients from overtreatment. Contrary to the literature, the present results implicate a clinical relevance of DFCI particularly in those who are physically highly active with localized pain on exertion. Structured physiotherapy as basic treatment is recommended.

Evaluation of the Effect of Photodynamic Therapy on CAM-Grown Sarcomas.

Resection margin adequacy plays a critical role in the local control of sarcomas. Fluorescence-guided surgery has increased complete resection rates and local recurrence-free survival in several oncological disciplines. The purpose of this study was to determine whether sarcomas exhibit sufficient tumor fluorescence (photodynamic diagnosis (PDD)) after administration of 5-aminolevulinic acid (5-ALA) and whether photodynamic therapy (PDT) has an impact on tumor vitality in vivo. Sixteen primary cell cultures were derived from patient samples of 12 different sarcoma subtypes and transplanted onto the chorio-allantoic membrane (CAM) of chick embryos to generate 3-dimensional cell-derived xenografts (CDXs). After treatment with 5-ALA, the CDXs were incubated for another 4 h. Subsequently accumulated protoporphyrin IX (PPIX) was excited by blue light and the intensity of tumor fluorescence was analyzed. A subset of CDXs was exposed to red light and morphological changes of both CAMs and tumors were documented. Twenty-four hours after PDT, the tumors were excised and examined histologically. High rates of cell-derived engraftments on the CAM were achieved in all sarcoma subtypes and an intense PPIX fluorescence was observed. PDT of CDXs resulted in a disruption of tumor-feeding vessels and 52.4% of CDXs presented as regressive after PDT treatment, whereas control CDXs remained vital in all cases. Therefore, 5-ALA mediated PDD and PDT appear to be promising tools in defining sarcoma resection margins (PDD) and adjuvant treatment of the tumor bed (PDT).

Effects of an Exercise Intervention on Gait Function in Young Survivors of Osteosarcoma with Megaendoprosthesis of the Lower Extremity-Results from the Pilot Randomized Controlled Trial proGAIT.

Limb preservation with megaendoprosthesis in adolescents and young adults (AYA) with bone tumors is associated with functional limitations and gait abnormalities. The proGAIT trial evaluated the effectiveness of an exercise program on gait function and quality of life, functional scales (MSTS, TESS), functional mobility, and fatigue as secondary outcomes. Eleven AYA survivors of malignant osteosarcoma with a tumor endoprosthesis around the knee (mean age: 26.6 (±8.4) years) were randomized into an intervention group receiving an 8-week exercise program or into a control group. Gait function was assessed via 3D motion capture and analyzed using the Gait Profile Score (GPS) and the Gait Deviation Index (GDI). GDI and GPS scores of participants suggest deviations from a healthy reference group. The exercise intervention had small-to-medium positive effects on gait score GDI |d| = 0.50 (unaffected leg), |d| = 0.24 (affected leg), subjective functional scores TESS |d| = 0.74 and MSTS |d| = 0.49, and functional tests TUG and TUDS |d| = 0.61 and |d| = 0.52. None of these changes showed statistical significance. Promising intervention effects suggest that regular exercise could improve lower limb function and follow-up care for survivors; however, a powered RCT as a follow-up project needs to confirm the pilot findings.

Pathological Fractures in Benign Bone Lesions - Diagnosis and Therapy. / Die pathologische Fraktur bei benignen Knochenläsionen - Diagnostik und Therapie.

INTRODUCTION: Most tumour-related pathological fractures occur in patients with bone metastases. However, in mostly younger patients, a pathological fracture can be due to both a benign or a malignant bone tumour. Making the correct diagnosis from among these two differential diagnoses is enormously important. If the tumour is malignant, treating the fracture inevitably leads to tumour cell contamination and can significantly worsen the oncological situation. The aim of this review article is firstly to provide the reader with diagnostic assistance in the case of suspected pathological fractures, and secondly to focus on the treatment of pathological fractures occurring with benign bone tumours. METHODS: This is a non-systematic review of the diagnosis and treatment of pathological fractures in benign bone tumours or tumour-like lesions, based on an electronic PubMed database search. We also present our own procedures, in particular for ruling out a malignant bone tumour. RESULTS AND DISCUSSION: Whenever a fracture occurs in the absence of sufficient traumatic force, the possibility of a pathological fracture should always be considered. As well as taking a general history for a possible primary tumour, it is particularly important to ask the patient whether they had any pain before the fracture occurred. If the findings from clinical examination or conventional radiological imaging give rise to suspicion of a pathological fracture, an MRI of the affected skeletal section with contrast medium should be carried out before commencing any fracture treatment. A CT scan is also helpful for accurately assessing bone destruction. If a malignant or locally aggressive benign bone tumour such as giant cell tumour (GCT) or aneurysmal bone cyst (ABC) cannot be definitively ruled out through imaging, a biopsy is essential. The bone biopsy must always be carried out on the assumption that the histological work-up will reveal a malignant bone tumour; it must therefore be performed according to strict oncological criteria. If the radiological diagnosis is unambiguous, e. g., a juvenile bone cyst (JBC) or a non-ossifying fibroma (NOF), conservative treatment of the fracture can be considered, depending on the location. In the presence of a locally aggressive benign bone tumour such as a GCT or ABC, curettage of the tumour must be carried out as well as treating the fracture. With GCT in particular, neoadjuvant therapy with denosumab prior to curettage and osteosynthesis or en bloc resection of the tumour should be considered, depending on the extent of the tumour. CONCLUSION: Pathological fractures, especially in younger patients, should not be overlooked. Only after a malignant or benign locally aggressive bone tumour has been definitively ruled out should fracture treatment be performed. In the presence of a locally aggressive bone tumour, as well as treating the fracture, it is usually necessary to perform curettage of the tumour - also en bloc resection, where applicable, in the case of a GCT. Depending on the location, benign, non-aggressive tumours can be treated conservatively if necessary.

5-ALA-mediated fluorescence of musculoskeletal tumors in a chick chorio-allantoic membrane model: preclinical in vivo qualification analysis as a fluorescence-guided surgery agent in Orthopedic Oncology.

BACKGROUND: Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) and other contrast agents has shown its efficacy in improving resection margins, local recurrence and survival rates in several medical disciplines. It is the objective of this study to analyze the engraftment rate of musculoskeletal tumor specimens on the chick chorio-allantoic membrane (CAM), the rate of tumor fluorescence (PDD), and the effects of photodynamic therapy (PDT) after exposure of tumors to 5-ALA in an in vivo environment. METHODS: A total of 486 CAMs were inoculated with macroscopic tumor grafts (n = 26; n = 478 eggs) and primary cell culture suspensions (n = 2; n = 8 eggs) from 26 patients on day 10 of egg development. On day 16, 2 mg/200 µl 5-ALA were topically applied per egg. After 4 h of incubation, Protoporphyrin IX was excited using blue light (420 ± 10 nm). Tumor fluorescence (PDD) was photo-documented. A subgroup of specimens was additionally exposed to red light (635 nm ± 10 nm; PDT). After the termination of the experiment, CAM-grown tumors were histopathologically analyzed. RESULTS: Benign and borderline tumors (chondroblastoma, giant cell tumor of bone and atypical chondrogenic tumor) presented with high rates of detectable fluorescence. Comparable results were found for chondrosarcoma, osteosarcoma and Ewing's sarcoma among bone and dedifferentiated liposarcoma, myxofibrosarcoma and undifferentiated pleomorphic sarcoma among soft tissue sarcomas. Overall, tumor fluorescence was negative for 20.2%, single-positive (+) for 46.9% and double-positive (++) for 32.9% of macroscopic xenografts, and negative in 20% and (+) in 80% of primary cell culture tumors. Macroscopic tumor xenografts (n = 478) were identified as viable in 14.8%, partially viable in 2.9% and partially to completely regressive in 45.2%. All (n = 8) tumors grown from primary cell culture were viable. After PDT, tumor samples were found viable in 5.5%, partially viable in 5.5% and partially to completely regressive in 68%. Egg survival increased with decreasing PDT doses. CONCLUSIONS: The CAM model proves to be a suitable in vivo model for the investigation of short-term observation questions in musculoskeletal tumors. The findings of this study warrant further investigation of PDT effects on musculoskeletal tumors and a possible incorporation of 5-ALA FGS in clinical Orthopedic Oncology care.

Transcriptome-Wide Gene Expression Profiles from FFPE Materials Based on a Nuclease Protection Assay Reveals Significantly Different Patterns between Synovial Sarcomas and Morphologic Mimickers.

BACKGROUND: Transcriptome profiling provides large data on tumor biology, which is particularly valuable in translational research and is becoming more and more important for clinical decision-making as well. RNA sequencing is considered to be the gold standard for this. However, FFPE material, as the most available material in routine pathology, has been an undefeatable obstacle for RNAseq. Extraction-free nuclease protection assays have the potential to be a reliable alternative method for large-scale expression profiling. The aim of this study was to validate and test the basic feasibility, technical applicability robustness, and reliability of the HTG transcriptome profiling (HTP) assay on clinical tumor samples. METHODS: FFPE samples from 44 synovial sarcomas (SyS) and 20 spindle cell sarcomas (SpcS) were used. The HTP assay was performed on 10 µm thin FFPE slides. After nuclease protection in the HTG Edge Seq System, libraries were generated for sequencing on an Illumina NextSeq 500 platform. Fastq data were parsed and then analyzed by using the HTG analysis platform EdgeSeq REVEAL. Immunohistochemistry was performed to validate the expression of TLE1. RESULTS: The technical application of the HTP Panel revealed robust and reliable results with 62 samples, and only 2 samples failed due to an incomplete digestion of gDNA. The analysis, performed at the analysis platform REVEAL, showed 5964 genes being significantly differentially expressed between SpcS and SyS. In particular, overexpression of the known marker TLE1 in synovial sarcoma could be recovered, which underlines the reliability of this system. DISCUSSION: Transcriptome profiling gets more and more important for tumor research and diagnostics. Among other established technologies, the HTP Panel has shown to be a feasible method to get robust and reliable results. Thereby, this method needs very few sample-input by getting a success-rate of 96.88%, which indicates the upper average range, compared to other technologies working with FFPE tissue. CONCLUSION: The nuclease protection assay-based HTP Panel is a feasible method for adequate transcriptome profiling with low sample input and therefore is suitable for further research of biomarkers.